This revision of a proposal submitted initially on 10/1/98 requests five years of support (10/1/01-9/30/06) to investigate the transition from experimental smoking to daily smoking and nicotine dependence and the underlying risk and protective factors among white, African-American and Hispanic adolescents. The research has five major goals: (1) To identify the timing and sequence of the transition from experimental smoking to daily smoking and nicotine dependence among adolescents. (2) To identify the psychological, social and biological factors that promote the progression to daily smoking and dependence and reduce the risk. Special attention will be paid to (a) depressive symptoms, (b) conduct problems, (c) initial differences in sensitivity to tobacco, (d) cotinine levels, and (e) exposure to prenatal smoking. (3) To specify the comorbidity and sequencing between daily smoking, nicotine dependence and psychiatric disorders. (4) To identify pathways of progression from experimental smoking to nicotine dependence and the use of illicit drugs. (5) To identify gender and ethnic differences among white, African-American and Hispanic youths with respect to Aims number 1-number 4. These aims will be achieved by conducting a five-wave two-year longitudinal follow-up of 1,275 6th-10th graders and their mothers. A two-stage research design will be implemented. In Phase I, approximately 17,000 students in grades 6-10 from selected public schools will be administered a brief survey. Responses will be used to select a target sample of 1,300 experimental smokers and 200 non-smokers, evenly divided among the three ethnic groups. In Phase II, 3 annual computerized household interviews will be conducted with 1,275 participating youths and their mothers, and 2 telephone interviews with the youths six months after the first and second household interviews. At each annual interview, a psychiatric assessment will be administered to the youth and the parent about the child; a saliva sample will be collected to determine cotinine levels, validate self-reports of smoking and predict progression to daily smoking and nicotine dependence. This study represents a rare attempt to investigate prospectively the periods of risk for nicotine dependence in adolescence, the duration from onset to dependence, and the factors that explain the transition to dependence. The study is unique in focusing on the comorbidity between smoking, nicotine dependence, and psychiatric disorders among adolescents of different ethnicity. The study will generate a unique understanding of the natural history, etiology and consequences of nicotine dependence among young people.